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Title: The stress-inducible protein DRR1 exerts distinct effects on actin dynamics
Author: Kretzschmar, Anja
Schülke, Jan-Philip
Masana Nadal, Mercè
Dürre, Katharina
Müller, Marianne B.
Bausch, Andreas R.
Rein, Theo
Keywords: Citosquelet
Proteïnes citosquelètiques
Cytoskeletal proteins
Issue Date: 11-Dec-2018
Publisher: MDPI
Abstract: Cytoskeletal dynamics are pivotal to memory, learning, and stress physiology, and thus psychiatric diseases. Downregulated in renal cell carcinoma 1 (DRR1) protein was characterized as the link between stress, actin dynamics, neuronal function, and cognition. To elucidate the underlying molecular mechanisms, we undertook a domain analysis of DRR1 and probed the effects on actin binding, polymerization, and bundling, as well as on actin-dependent cellular processes. METHODS: DRR1 domains were cloned and expressed as recombinant proteins to perform in vitro analysis of actin dynamics (binding, bundling, polymerization, and nucleation). Cellular actin-dependent processes were analyzed in transfected HeLa cells with fluorescence recovery after photobleaching (FRAP) and confocal microscopy. RESULTS: DRR1 features an actin binding site at each terminus, separated by a coiled coil domain. DRR1 enhances actin bundling, the cellular F-actin content, and serum response factor (SRF)-dependent transcription, while it diminishes actin filament elongation, cell spreading, and actin treadmilling. We also provide evidence for a nucleation effect of DRR1. Blocking of pointed end elongation by addition of profilin indicates DRR1 as a novel barbed end capping factor. CONCLUSIONS: DRR1 impacts actin dynamics in several ways with implications for cytoskeletal dynamics in stress physiology and pathophysiology.
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It is part of: International Journal of Molecular Sciences, 2018, vol. 19, num. 12, p. 3993
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ISSN: 1661-6596
Appears in Collections:Articles publicats en revistes (IDIBAPS: Institut d'investigacions Biomèdiques August Pi i Sunyer)
Articles publicats en revistes (Biomedicina)

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